The method for the treatment of cancer can be divided into a method of direct killing cancer cells such as surgery, administration of an anticancer agent, and irradiation; and a method of activating immune function in vivo to remove cancer cells such as immunotherapy. Conventionally, the method of direct killing has been mainly used, but recently, it has been used in combination with immunotherapy in the treatment of cancer.
Since the immune response mechanism was disclosed recently, many attempts have been made to treat cancer by using immunomodulators. Immunomodulators stimulate immune cells in vivo nonspecifically to enhance the immune function, thereby increasing the body's defense against disease factors. Such nonspecific immunomodulators are exemplified by killed bacterial bodies, chemically synthesized substances (synthesized nucleic acid derivatives or glycosides), and biological agents (cytokines or hormones), etc. Studies are being made to obtain anticancer effect by increasing in vivo immune function by administering the said materials above. However, most of those nonspecific immunomodulators are limited in clinical use because of toxicity or side effects. In particular, since various cytokines involved in immune response were identified, studies to mass produce those cytokines by genetic engineering method and apply them to cancer therapy have been actively undergoing. However, the studies are limited because of a severe toxicity caused thereby. In the course of cancer treatment via using an anti-cancer agent or radio-therapy, severe side effects such as hematopoietic disorder and self-renewal tissue damage can be accompanied. Such side effects are attributed to oxidative tissue damage caused by the anticancer agent or radiation.
As a study on substances that can protect a living body from radiation, there was a report made in 1949 saying that cystein containing thiol group displays the radioprotective effects. Since then, aminothiol derivatives (especially WR series) have been studied intensively. However, because of the toxicity of aminothiol derivatives, the practical application has been limited. Thereafter, the protective effects of chemical synthetics such as dipyridamole, adenosine monophosphate, and deoxyspergualin have been studied, but they have also been limited in practical application due to toxicity. Another attempt has been made to obtain the protective effect by stimulating hematopoietic and immune system using polysaccharides such as glucan and detoxified bacterial bodies such as OK-432, which have been studied as anticancer immunomodulators. However, they are also limited in practical use due to side effects. It is tried recently to obtain the radiation protection effect by using cytokines involved in immune response and hematopoietic function including interleukin-1, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (GM-CSF), hormones. However, these agents are also applied limitedly due to toxicity.
Therefore, it is urgently requested to develop a safe material that can increase anticancer effect, immune function, and hematopoietic function and at the same time can protect a living body from side effects caused by irradiation. Recent studies are focused on natural bioactive substances without side effects. In particular, since oxidative damage caused by harmful reactive oxygen species or free radicals as well as radiation or chemical substances has been revealed as a cause of various diseases such as aging-related diseases and cancer, studies are undergoing with antioxidants to prevent and treat these diseases. Bioactive substances efficient in body regulation and protection have been screened actively from natural substances and some of them are now commercialized as health supplementary foods or therapeutic agents.
Korean Patent No. 10-0506384 describes about the herbal composition and its preparation method of herb mixture for cancer inhibition, recovery of immune system and protection of body from oxidative damage, wherein an herbal composition prepared from a herb mixture comprising Angelica Radix, Cnidium Rhizoma, and Paeonia Radix was confirmed to demonstrate the anticancer effect, immune function improvement effect, hematopoietic function improvement effect, and radiation protection effect. However, the herbal composition was prepared only by the hot water extraction method. So, the content of fat-soluble polyphenols in the composition was low, suggesting that the composition did not have sufficiently high medicinal effect for the inhibition of cancer cell growth and the prevention of side effects caused by anticancer agents and radiation.
The present inventors tried to develop an herbal composition with a more significant medicinal effect than the herbal composition of comparative example (Korean Patent No. 10-0506384) by increasing the content of fat-soluble polyphenols. In the course of our study, unlike the herbal composition of comparative example developed based on the hot water extract, the inventors believed that the composition based on the aqueous ethanol extract prepared by appropriate ethanol concentration could have significantly increased fat-soluble polyphenols while maintaining the water-soluble polyphenol content at the similar level. Based on the thought, the present inventors prepared an herbal composition capable of exhibiting various activities together and proving their excellent activity, leading to the completion of the present invention. Briefly, the inventors mixed Angelica Radix, Cnidium Rhizoma, and Paeonia Radix, resulting in the preparation of an herb mixture. A certain portion of herb mixture aqueous ethanol extract was taken and stored. The remaining portion of the herb mixture aqueous ethanol extract, and the hot water extract were mixed, followed by ethanol precipitation. The precipitated polysaccharides were mixed with the stored portion of aqueous ethanol extract to prepare the herbal composition. (It will be described in detail in examples). The herbal composition comprising the polysaccharides above and the aqueous ethanol extract contains the significantly higher content of fat-soluble polyphenols including decursin, and shows more significant anti-oxidative activity and immune cell activation effect, inhibits cancer cell growth, significantly reduces renal toxicity and liver toxicity caused by the anticancer agent cisplatin almost back to the normal level, and has a significant inhibitory effect on intestinal crypt loss caused by irradiation, by confirming which the present inventors completed this invention.